Pregnancy‐related knowledge in women with epilepsy in childbearing age: A pilot questionnaire survey from China

Abstract Purpose We aim to understand the knowledge of and attitudes toward pregnancy issues among women with epilepsy (WWE) and their caregivers and analyze the answers from the questionnaire to expose topics that require educational activities; thus, WWE experiences pregnancy better. Methods WWE at their childbearing age and/or their caregivers who entered the Fourth Affiliated Hospital of Zhejiang University for treatment of their condition were invited to fill out a questionnaire between March 1 and November 31, 2022. Results A combined total of 205 WWE and 142 caregivers completed the questionnaires. Among the surveyed WWE, a majority (63.74%) reported experiencing at least one miscarriage or induced abortion. However, a significant proportion (84.62%) of these WWE were still able to successfully give birth to at least one child. Furthermore, the offspring of these WWE showed no significant differences compared to the offspring of women without epilepsy, as reported by 93.51% of the participants. The participants’ knowledge regarding the impact of epilepsy on pregnancy was found to be comparable, with average scores of 7.74 and 7.84, respectively. The participants exhibited a limited comprehension of antiseizure medications (ASMs)‐related knowledge, specifically pertaining to ASMs adjustment during pregnancy (17.56% vs. 16.90%) and offspring outcomes (30.24% vs. 26.06%). Statistical analysis revealed significant correlations between the overall score and education level (p < .001), as well as epilepsy duration (p = .008). Regarding the source of knowledge, participants acknowledged primarily relying on neurologists, who remained their preferred choice for consultation. Conclusion In our study, the understanding of pregnancy‐related knowledge did not differ from WWE and their caregivers, both are far from satisfactory in certain areas. It is urgent for WWE and their caregivers to improve their pregnancy‐related knowledge of epilepsy. As their primary access is from knowledgeable health care professionals like neurologists, well‐trained neurologists in epilepsy management during pregnancy are in need.


INTRODUCTION
Epilepsy is a prevalent chronic neurological disorder globally, with an estimated lifetime prevalence of 6.85 cases per 1000 women (Fiest et al., 2016).A significant proportion of women affected by epilepsy are of childbearing age and thus encounter gender-specific challenges, particularly during pregnancy.Although the majority of women with epilepsy (WWE) experience uneventful pregnancies, deliveries, and successful childbirth, research has demonstrated an increased risk of pregnancy complications and adverse offspring outcomes (Stephen et al., 2019).Notably, studies have revealed that over 1.3 million WWE in the United States are currently in their reproductive years (Li et al., 2021).Despite the limited availability of Chinese demographic data, the implications of managing epilepsy during pregnancy for WWE, their families, medical practitioners, and society at large are significant, particularly in light of China's vast population and the gradual implementation of the two-and three-child policy.
In China, it is customary for unmarried women to reside with their parents.Chinese parents possess a longstanding tradition of providing care for their offspring, irrespective of their age, particularly as WWE are in a disadvantaged position.Consequently, the perceptions of WWE may be partially shaped by the influence of their parents.Upon entering into matrimony, WWE and their partners assume joint responsibility for procreation.Given that epilepsy can potentially impair cognitive and social abilities of WWE, spouses are required to assume a heightened level of responsibility, including acquiring a comprehensive understanding of pregnancy-related cognition.
Given these complex considerations, preconceptual counseling plays a pivotal role in the management of WWE, especially regarding effective birth control, planned pregnancies, and antiseizure medications (ASMs) optimization.However, a study in the USA has shown that half of the pregnancies in WWE are unplanned (Johnson et al., 2018).Thus, it is essential to know the conception of pregnancyrelated knowledge in WWE and their caregivers and to take regular preconceptual counseling.
Accordingly, the aims of this study were as follows: (1) conduct a questionnaire survey to understand if WWE and their caregivers have comparable knowledge of and attitudes toward pregnancy issues, (2) try to analyze the answers from the questionnaire to expose topics that require future educational activities.

MATERIALS AND METHODS
This is a single-center study conducted in the Fourth Affiliated Hospital, Zhejiang University School of Medicine from March 1 to November 31, 2022.The ethics committees of The Fourth Affiliated Hospital, Zhejiang University School of Medicine approved all the procedures (K2022055).The participants provided informed consent after being briefed on the study's objectives and guaranteed confidentiality.Participants were also granted the prerogative to dissent from participation and discontinue their involvement at any given point.

Participants and definitions
All consecutive WWE and/or their caregivers who entered the epilepsy of the outpatient or inpatient department and met the inclusion criteria were subjected to in-person interviews.Caregivers were defined as family caregivers who accompany WWE to the clinic and live together for at least 3 months after their patients were diagnosed with "epilepsy."Participants are required to enter a designated room and subsequently scan a QR code to complete an electronic questionnaire.After completing the questionnaire, a self-written brochure about pregnancy-related knowledge was distributed to them with personalized education guidance and the general feedback was positive.
The inclusion criteria were as follows: (1) were at their childbearing age, which we set the age at 18-49 years in our study according to Chinese social demography; (2) were diagnosed with epilepsy for more than 1 year which met the diagnostic criteria of revised 2014 definition of the International League Against Epilepsy (Fisher et al., 2014); (3) informed consent obtained.Patients were excluded if they had a history of mental retardation or uncontrolled psychosis, or if they were unable to understand the questionnaires.For those caregivers with informed consent who were asked to fulfill the questionnaire, they should be (1) at least 18 years old; (2) understand the questionnaires; (3) the WWE with whom they accompany should meet the aforementioned inclusion criteria at the same time.

Questionnaire on demographics and clinical data
Part one of the questionnaire was custom-designed for this study to collect information.The questionnaire that was to be administrated to WWE comprised three sections: (1) demographic data (age, education level); (2) personal information about pregnancy (e.g., contraceptive methods, history of pregnancy, miscarriage or abortion, and delivery); (3) history of epilepsy (e.g., age of epilepsy onset; present frequency of seizures; type of seizure; present ASMs prescribed).As patients had to fulfill their history of epilepsy with/without their caregivers' help, the type of epilepsy was simply classified as with impaired awareness or not.For those patients with both types of seizure, they were asked to choose the option of with impaired awareness if they lost consciousness in the last 12 months.
The other questionnaire, which was to be administrated to caregivers, only comprised two questions about their identity and education level to increase the response rate of the questionnaire.

3.2.2
Questionnaire on pregnancy-related knowledge Part two of the questionnaires was largely analogous in both two groups, which consisted of 13 single-choice questions and three multiple-choice questions about pregnancy-related knowledge.Each single-choice question was designed to offer three or four potential response options, of which only one was considered accurate based on current medical knowledge, with the exception of question 7.As patients were directed to keep seizure-free for 12 months at least before pregnancy in practice in China while studies figured out that keeping seizure-free for at least 9 months is ideal before pregnancy (Metcalfe et al., 2012), we set both options as a correct answer.Those 13 single-choice questions are scored on the basis of the principle of awarding one point for correct responses and no points for incorrect ones.Patients were instructed to indicate the options they deemed most suitable.Additionally, the final three multiple-choice questions were open-ended and not included in the scoring process.

Statistical analysis
The statistical analysis was conducted using SPSS version 26.In the surveyed WWE, it was found that 21.96% did not utilize any form of contraception, whereas 3.41% relied on oral contraceptives.
The WWE group was evenly divided between those with a history of pregnancy and those without (50.24%vs. 49.76%).In the former group, a significant proportion (63.74%) reported experiencing at least one instance of miscarriage or induced abortion.However, the majority (84.62%) still successfully gave birth to one or more children, and only 6.49% of the offspring displayed abnormalities in their reproductive development or intelligence.Detailed data are presented in Table 2.

Pregnancy-related knowledge
The median scores of questionnaires for WWE and caregivers were 7.74 and 7.84, respectively, as shown in Table 3.Among these two a Calculate the scores for question1-13 in the questionnaire.
surveyed groups, the highest percentage of correct answers was observed for questions 5 (informed obstetrician of a history of epilepsy: 97.56% vs. 95.07%)and 4 (prenatal consultation: 92.20% vs. 96.48%).However, when examined for a more detailed understanding of the impacts, they demonstrated poor performance (16%-78% accuracy).In both groups, the issues of ASM adjustment during pregnancy, offspring birth outcomes, pregnancy complications, and breastfeeding are the most problematic.
Besides, an evaluation was conducted to determine if the accuracy of the 13 questions was influenced by prior pregnancy experience.
The findings revealed that a higher percentage of women with a history of pregnancy correctly answered question 6 regarding folic acid supplementation (76.70% vs. 54.90%,p < .001).Conversely, a greater proportion of women without pregnancy experience correctly answered question 13 regarding breastfeeding (40.78% vs. 49.02%,p < .001).No significant association was observed between two groups in the remaining 11 questions.
Furthermore, our research investigates the influence of sociodemographic variables, disease advancement, and social role on the questionnaire score.Moreover, we analyze the correlation between score and sociodemographic factors, along with the frequency of seizure types, as presented in Tables 4 and 5, correspondingly.Only some certain weak but statistically significant relationships existed: positive with educational level (p < .001)and epilepsy duration (p = .008).

DISCUSSION
We conducted a questionnaire survey among those WWE and/or caregivers who entered our outpatient or inpatient epilepsy clinic to seek medical care.The key findings of our study were as follows:   (Wang & Jiang, 2022).Previous studies (Mostacci et al., 2018;Viale et al., 2015) have indicated an elevated likelihood of spontaneous miscarriage among WWE; however, our investigation revealed a significantly higher rate of fetal loss in WWE compared to another study that reported an abortion rate of 11.5% (Mostacci et al., 2018).The factors contributing to the elevated rate of abortion in WWE align with those general Chinese women in some certain (Wang & Jiang, 2022).

Fertility status of the surveyed WWE
Nevertheless, the limited utilization of contraceptives could potentially be a contributing factor to the elevated incidence of abortion in WWE.In our study, it was found that among 177 WWE, only 132 individuals were found to utilize effective contraceptives, which was lower than the reported contraceptive usage rate of 79.2% within the general population of China (Haakenstad et al., 2022)

Perception of pregnancy-related knowledge among participants
There was a lack of statistically significant disparity observed between WWE and caregivers in terms of their scores and unknown incidence, except for the domain of prenatal consultation, where the latter group performed better.Despite patients having higher levels of education compared to caregivers (p < .001),both groups appeared a limited comprehension of pregnancy-related knowledge.
Both patients and caregivers demonstrated a high level of agreements (>90%) on disease informing obstetricians as well as prenatal consultation.This indicates that both groups comprehended the potential adverse consequences of epilepsy and/or ASMs on their own well-being and the health of their future offspring.However, upon further inquiry, it became evident that neither of the two groups pos-sessed a comprehensive understanding of the appropriate adjustment pattern for ASMs.In spite of variations in the options available, prior research conducted in Poland and Canada (Jędrzejczak et al., 2020;Metcalfe et al., 2012) has demonstrated that a majority of WWE were aware of the fluctuating clearance of ASMs during pregnancy.
These findings highlight the necessity of seeking professional guidance to appropriately adjust ASM dosages.The precise cause of this phenomenon remains uncertain, with potential explanations including the following: (1) A significant disparity in medical accessibility and public health education between developed and developing countries.
(2) Underestimated negative consequence of epileptic seizure during pregnancy: generalized tonic-clonic seizures lead to maternal hypoxia, lactic acidosis, and fetal asphyxia during pregnancy (Haakenstad et al., 2022), let alone increased frequency of seizures during pregnancy (Pennell et al., 2020).(3) Overestimated of the negative effect of ASMs on the fetus: Past research had suggested that fetal exposure to ASMs heightened the likelihood of major congenital malformations.However, a recent study has demonstrated that, with appropriate selection of ASMs, there was no significant disparity in fetal loss or major congenital malformations between WWE and the control group.The only exception was the occurrence of fetal loss, which was influenced by the level of ASMs and attributed to ASMs polytherapy (Razaz et al., 2017).Indeed, the ASMs most commonly prescribed in our study include levetiracetam, lamotrigine, and oxcarbazepine.The teratogenicity of these ASMs was found to be comparable to that of the untreated group (Tomson et al., 2018).It is imperative that their health care providers comprehend the advantages of utilizing the appropriate type and dosage of ASMs to mitigate the risk of epileptic seizures during pregnancy, thereby benefiting both the WWE and their offspring.
However, a significant proportion of the participants exhibited a tendency to underestimate the prevalence of adverse birth outcomes and pregnancy complications.This perspective can potentially be attributed to the inclination to implement misguided notions, such as reducing the dosage of ASMs or completely discontinuing their usage.
The occurrence of epileptic seizures during pregnancy is correlated with heightened probabilities of unfavorable pregnancy and perinatal consequences (Razaz et al., 2017).Conversely, the utilization of ASMs during pregnancy is generally not associated with adverse maternal and fetal or neonatal outcomes, with the exception of its potential teratogenic effects.
Previous observational studies have established that the seizurefree duration prior to pregnancy is a significant determinant in a People who select "No" or "I don't Know in question 3" will skip this question.b We also make "12 months" as correct answer as patients were directed to keep seizure-free for 12 months at least before pregnancy in practice.
forecasting the likelihood of remaining seizure-free during pregnancy (Battino et al., 2013;Vajda et al., 2008).However, it is noteworthy that only a limited proportion of patients and caregivers (44.38% and 59.82%, respectively) possessed knowledge regarding the specific duration in our study.
Not only intrauterine exposure but also breastfeeding while receiving ASMs is a significant concern for WWE, leading to a lower percentage of WWE breastfeeding their children compared to the general population (Meador et al., 2014).Previous survey findings indicate that most neurologists in our region are aware of the recommendation to encourage breastfeeding in WWE undergoing ASM monotherapy (Xu et al., 2022).However, our study found that only approximately half of WWE and their caregivers (45.51% and 53.57%, respectively) acknowledged the benefits of breastfeeding outweighing the drawbacks, which was not satisfactory yet.
It is imperative for Chinese neurologists to provide related information to these WWE and their caregivers once WWE reach sexual maturity.Furthermore, it is highly encouraged to foster close collaboration and communication between obstetric professionals in order to promote optimal care for these individuals.

Incomprehensive and de-normalized treatment in China
Over 90% of patients and their caregivers acknowledged that their knowledge regarding pregnancy-related matters primarily stemmed from their neurologists, and publication of Chinese guidelines on the management of WWE during periconceptional period highlights the endorsement of vaginal delivery and folic acid supplementation (Group of Electroencephalography and Epilepsy, Branch of Neurology, Chinese Medical Association, 2021).However, the findings revealed that only approximately 50%-60% of the individuals surveyed provided accurate responses, indicating the need for further improvement.
In our study, 27 WWE, all of whom were within the reproductive age range, were observed to be using VPA.Although certain WWE may resort to VPA due to the ineffectiveness of alternative ASMs, a notable percentage of women employ VPA as a consequence of neu-rologists' limited awareness regarding its detrimental consequences.This particular ASM is recognized as a teratogen and has been linked to adverse outcomes in offspring (Tomson et al., 2018).It is noteworthy that the Food and Drug Administration has persistently emphasized the necessity of a "black box" warning for this drug.Furthermore, it is noteworthy that over 90% of individuals express a desire to obtain additional information from their health care professionals.However, it is important to acknowledge that only a minority of doctors consistently offer guidance on pregnancy for WWE, in contrast to the majority who provide information upon patient request (Xu et al., 2022).This observation could potentially indicate suboptimal doctor-patient communication, potentially resulting from a focus on maximizing efficiency.Given the high turnover rate in Chinese clinics, the utilization of an online tool, as previously developed by Zelano's group (Lisovska et al., 2021) would be an ideal approach for WWE to access information at any time and location, thereby enhancing patient education and facilitating improved communication.

Factors related to knowledge
Contrary to previous research (Dierking et al., 2018;Metcalfe et al., 2012), which failed to establish a significant association between prior pregnancy experience and knowledge, our study reveals that individuals with previous pregnancy experience exhibit superior adherence to folic acid supplementation.This outcome may be attributed to their personal experiences.In contrast to the findings of a previous study (Jędrzejczak et al., 2020), which indicated that women with prior pregnancy experience exhibited a more favorable response to the inquiry regarding breastfeeding, our study revealed that women without prior pregnancy experience demonstrated superior performance.
This observation may be attributed to their own experiences, misguided and outdated.Consequently, it is crucial to provide WWE and caregivers with up-to-date knowledge pertaining to pregnancy-related matters.
The study has successfully identified the factors that exhibited a statistically significant impact on the score, namely, the education level and epilepsy duration.The previous research (Friedrich et al., 2018;Jędrzejczak et al., 2020) has consistently reported a positive correlation between knowledge and education, which is further supported by our findings.In contrast to prior studies that indicated no association between epilepsy duration and pregnancy-related knowledge (Metcalfe et al., 2012), our study reveals a weak yet statistically significant relationship between the score and epilepsy duration.This

CONCLUSION
In our study, it was observed that both WWE and caregivers exhibited a lack of satisfactory pregnancy-related knowledge in certain domains.
Although they demonstrated awareness regarding the significance of preconception counseling and disclosing medical history, their limited (1) Approximately half of WWE in our study possessed a prior pregnancy record, and the majority achieved successful deliveries.(2) The most com-monly prescribed ASMs were levetiracetam, lamotrigine, and oxcarbazepine.Notably, nearly one in six WWE still use VPA.(3) Participants' pregnancy-related knowledge of epilepsy was comparable and did not reach the desired level yet, the most problematic questions were ASMs adjustment during pregnancy and offspring outcomes.(4) Most of participants admitted their pregnancy-related knowledge primarily came from neurologists, and neurologists remained their preferred source for consultation.(5) Education level and epilepsy duration had an independent association with the score of questionnaires in WWE.
phenomenon can be attributed to the enhanced availability of information, enabling individuals with longer durations of epilepsy to acquire more knowledge about their condition.This suggests that participants primarily acquired pregnancyrelated knowledge through their own initiative rather than through guidance from health care professionals.Epilepsy is one of the most common neurological diseases worldwide, nearly 80% of patients live in low-and middle-income countries, including China.Although the World Health Organization has emphasized the need to prioritize epilepsy within global public health agendas (World Health Organization, 2019), the availability of comprehensive health care system data in China remains inadequate.Consequently, policymakers face challenges in guaranteeing widespread dissemination of epilepsy-related knowledge.Our study offers a valuable point of reference for the future development of health literacy in China.
Clinicodemographic characteristics of participants.
In our study, 50.24% of WWE had a history of pregnancy.This finding aligns closely with the reported the prevalence of pregnancy history among women of childbearing age in China, which reported a rate of 54.1% (Institute of Fudan University Health Communication, 2022).the general female population in China (99.47% incidence) (Institute of Fudan University Health Communication, 2022).Additionally, our survey findings indicate a 63.74% occurrence of abortions or miscarriages among the surveyed population, which potentially contributes to the observed lower birth rate.In our study, it was observed that TA B L E 2

If you/your relative plan to be pregnant, will you consult your doctor? .012
Questionnaire of pregnancy-related knowledge.

In your opinion, do women with epilepsy have a higher risk of complications during pregnancy compared to general populations
(e.g.bleeding, premature, cesarean birth)?

16. Where do you want to get more information about pregnancy-related knowledge in the future? (multi-choice)
Mean values of correct answers about seizure control, type of epilepsy, pregnancy experience, antiseizure medication (ASM) therapy, and social role.Correlation of pregnancy-related knowledge with demographic factors, history of epilepsy, and history of pregnancy.
a Independent sample t-test.bOne-way ANOVA.TA B L E 5 b Spearman's correlation coefficient.
comprehension of intricate details is concerning, particularly in relation to ASMs' adaptation during pregnancy.The inflated perception of risk associated with ASMs contributes to the inaccurate understanding of ASMs-related information, including offspring outcomes, pregnancy complications, and breastfeeding, which are areas of particular concern.Enhancing the knowledge of WWE and their support systems is crucial.Although pregnancy-related information is readily available through open-access sources, the primary source of information for WWE is health care professionals, particularly neurologists.Conse-Data curation; formal analysis; investigation.Yanlu Fu: Data curation; formal analysis; investigation.Beibei Shen: Data curation; formal analysis; investigation.Shuang Wang: Writing-review and editing; validation; supervision.Jiajia Fang: Writing-review and editing; funding acquisition; methodology; supervision; resources; project administration.
quently, it is imperative to have well-trained neurologists specializing in epilepsy management during pregnancy, supported by appropriate written materials.AUTHOR CONTRIBUTIONS Qiwei Li: Conceptualization; methodology; writing-review and editing; writing-original draft; validation; formal analysis; visualization; software; investigation; data curation.Yina Cao: Data curation; formal analysis; resources; investigation.Jingxin Zhang: